Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency
Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency
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DOI：
10.1007/s00223-002-1090-x
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发表时间：
2003-07-01
影响因子：
4.2
通讯作者：
Denhardt, DT
中科院分区：
文献类型：
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作者：
Shapses, SA;Cifuentes, M;Denhardt, DT
骨桥蛋白空小鼠先前显示具有含有更多矿物质和更大矿物质晶体的骨骼。这些骨被独立地观察到抵抗卵巢切除术诱导的重塑。为了将骨桥蛋白（一种矿物质晶体形成和生长的体外抑制剂）的理化作用与骨桥蛋白对体内骨重塑的作用分开，本研究检查了给予钙缺乏饮食的成熟（5个月大）骨桥蛋白缺失（Opn-/-）和野生型（WT）小鼠。生化指标测定在4周的钙缺乏，随后由I周的再喂养足够的钙。与Opn-/-小鼠相比，Ca缺乏引起WT中骨吸收的短暂增加（P = 0.01），而只有Opn-/-小鼠倾向于增加Ca吸收（P = 0.08），但两组均显示甲状旁腺激素（PTH）水平升高（P < 0.001）。在钙缺乏过程中，两组由于钙缺乏引起的骨形成标志物的升高相似。傅立叶变换红外显微光谱评估矿物性能在20微米的空间分辨率在不同的解剖区域的骨。与WT相比，Ca缺乏Opn-/-动物的矿物质含量略有增加，并且老年（骨内膜）骨的矿物质含量显著增加，这意味着破骨细胞募集受损。在除骨膜附近（较年轻的矿物质）以外的所有部位，钙缺乏Opn-/-骨的结晶度相对于钙缺乏WT增加。这些数据表明，骨桥蛋白具有物理化学效应（抑制晶体生长和晶体增殖）和破骨细胞募集的作用，在其缺乏的情况下，外骨骼器官维持钙稳态。
Osteopontin null-mice were previously shown to have bones containing more mineral and larger mineral crystals. These bones were independently seen to be resistant to ovariectomy-induced remodeling. To separate the physicochemical effects of osteopontin, which is an in vitro inhibitor of mineral crystal formation and growth, from effects of osteopontin on in vivo bone remodeling, this study examined mature (5-month-old) osteopontin-null (Opn-/-) and wildtype (WT) mice given a calcium-deficient diet. Biochemical parameters were measured during 4 weeks of Ca deficiency, followed by I week of refeeding adequate Ca. Ca deficiency caused a transiently greater rise in bone resorption in WT than Opn-/- mice (P = 0.01), whereas only the Opn-/- mice tended to increase Ca absorption (P = 0.08), yet both groups showed elevated levels of parathyroid hormone (PTH) (P < 0.001). The rise in markers of bone formation due to Ca deficiency was similar in both groups during Ca deficiency. Fourier transform infrared microspectroscopy assessed mineral properties at 20 mum spatial resolution in different anatomic regions of the bone. The Ca-deficient Opn-/- animals had slightly increased mineral content as compared to the WT, and there was a significant increase in the mineral content of older (endosteal) bone, implying that osteoclast recruitment was impaired. Crystallinity in the Ca-deficient Opn-/- bones was increased relative to the Ca-deficient WT at all sites except adjacent to the periosteum (younger mineral). These data suggest that osteopontin has both a physicochemical effect (inhibiting crystal growth and crystal proliferation) and a role in osteoclast recruitment, and in its absence, extraskeletal organs maintain calcium homeostasis.